Choanoflagellates and the Origin of Animal Multicellularity

Part 1: The origin of animal multicellularity

00:00:07.27 So, animals are incredible! 00:00:10.06 Some of them can fly through the air, 00:00:12.09 some of them can swim. 00:00:14.06 Animals have incredibly diverse body plans, 00:00:16.29 for instance this nudibranch. 00:00:19.13 Some of them can pattern their coloration 00:00:22.02 in different ways, 00:00:23.19 like this moth, 00:00:25.09 and even what we might consider simple organisms, 00:00:27.20 like the jellyfish that we see here 00:00:30.06 or a sponge... 00:00:32.22 these are incredibly interesting organisms as well, 00:00:35.11 and all of these animals share in common 00:00:37.16 something important, 00:00:39.02 which is they are composed of thousands and millions of cells 00:00:41.16 and these cells are working together 00:00:43.19 to make the organism work properly. 00:00:46.11 How did this all come to be? 00:00:48.16 Well, that's the focus of the talk 00:00:50.21 that I'm going to give you today. 00:00:52.12 The work in my laboratory has to do 00:00:54.03 with the origin of multicellularity. 00:00:56.12 My name is Nicole King. 00:00:58.01 I'm an investigator with the Howard Hughes Medical Institute 00:01:00.04 and a professor at the University of California at Berkeley, 00:01:02.23 and I'm excited to be here today 00:01:04.15 to tell you about my research. 00:01:06.18 Now, in the closing line of 00:01:09.25 Darwin's Origin of Species, 00:01:11.17 he remarked on endless forms most beautiful, 00:01:13.19 and he was referring to 00:01:16.28 the incredible diversity of body plans that we can see here, 00:01:19.10 and much of his research and thinking 00:01:22.14 had to do with trying to understand, 00:01:24.22 how do we get this diversity of organisms? 00:01:27.00 And there's been a great deal of progress in this regard, 00:01:29.24 largely from the work of embryologists 00:01:33.07 and evolutionary biologists 00:01:34.22 and geneticists working together 00:01:36.13 to try to understand what are the molecular 00:01:38.20 and mechanistic underpinnings 00:01:40.12 of the diversification of animal body plans. 00:01:43.07 But, in fact, there's something else important 00:01:45.14 that we need to keep in mind, 00:01:46.26 and that is that animals are united 00:01:48.21 by their shared ancestry. 00:01:50.08 They all share a common ancestor 00:01:51.27 that you can see here, indicated by this red dot. 00:01:55.07 And, in fact, we know relatively little 00:01:57.03 about the nature of that organism. 00:01:59.10 We don't know much about what its biology was like 00:02:01.21 or what its genome contained, 00:02:05.00 and we know even less 00:02:06.25 about the organisms from which it evolved, 00:02:09.05 but we can make some reasonable inferences 00:02:12.17 about the prehistory, 00:02:14.07 the pre-metazoan history of animals. 00:02:16.15 What we can reasonably infer 00:02:19.01 is that there some important evolutionary processes 00:02:22.05 that predate animal origins, 00:02:24.16 and these have to do with the origin of multicellularity, 00:02:27.22 the transition from a single-celled lifestyle 00:02:30.09 to one with organisms that were capable 00:02:33.07 of being multicellular 00:02:35.15 and coordinating the activities 00:02:37.07 of their different cells. 00:02:38.28 So, what I'd like to talk to you about today, 00:02:40.23 in this first part of my talk, 00:02:42.29 is what are the big questions that we want to ask 00:02:45.23 when we want to think about reconstructing animal origins, 00:02:49.25 and I think there are some discrete questions 00:02:51.27 that we can start to address. 00:02:53.26 The first is: 00:02:55.24 how did genome evolution contribute to animal origins? 00:02:59.07 It's clearly the case 00:03:01.21 that different groups of organisms on the tree of life 00:03:04.21 have different types of genes in their genomes, 00:03:07.03 and what we're interested in in my lab 00:03:09.10 is trying to understand how changes in gene sequences 00:03:12.17 and the composition of genomes 00:03:15.10 might have contributed to animal origins. 00:03:17.06 In addition, we're interested in understanding 00:03:19.21 how genes that are required for animal development 00:03:22.09 might have functioned before animals first evolved. 00:03:26.13 One of the special things about animals 00:03:28.08 is they have different cell types 00:03:30.15 that are not found in other groups of organisms. 00:03:32.23 These might include neurons 00:03:34.20 or the epithelial cells that make up your skin 00:03:37.01 and the lining of your gut. 00:03:38.28 How did those specialized cell types first evolve? 00:03:42.25 And then, in a topic that 00:03:45.29 we didn't expect to be studying, 00:03:47.20 we find that we're becomingly increasingly interested 00:03:49.24 in how interactions with bacteria 00:03:51.21 might have influenced animal origins, 00:03:53.19 and I'm gonna come back to that topic in part two. 00:03:56.27 And, of course, in the background of all of this 00:04:01.01 we're interested in understanding 00:04:03.23 the evolutionary implications of multicellularity, 00:04:05.21 and this is a topic of research that is ongoing. 00:04:12.00 Now, historically, 00:04:14.12 we've been very interested... 00:04:16.15 evolutionary biologists 00:04:18.29 have approached the evolution of animals 00:04:21.00 and the diversification of body plans 00:04:23.01 by really focusing on the fossil record, 00:04:25.12 and fossils have been great. 00:04:26.26 They tell us about the age of certain animal groups 00:04:29.03 and they can tell us about the shapes 00:04:31.07 of some of their body parts. 00:04:33.24 So, for instance, these beautiful star-shaped objects 00:04:36.21 are actually spicules from an ancient sponge, 00:04:39.27 this is a hypothesized embryo 00:04:43.08 that has recently been recovered, 00:04:45.20 and here we have a fossil of a coral, 00:04:47.17 and so we can see the fossil remnants of animals, 00:04:50.24 but it really doesn't tell us the whole story. 00:04:52.20 It doesn't tell us how animals came to be 00:04:55.02 and it doesn't tell us how cells 00:04:57.23 in those ancient organisms actually interacted. 00:05:01.18 To really understand animal origins, 00:05:03.15 I think we need to be focusing 00:05:05.20 on comparing living organisms, 00:05:07.13 and so what I'm going to tell you in this first part 00:05:09.22 of my iBio seminar 00:05:11.17 is about an unusual group of organisms 00:05:13.15 called the choanoflagellates 00:05:14.29 and how they can give us special insight into animal origins. 00:05:18.21 And then I'm going to tell you about 00:05:20.23 how the study of choanoflagellates, 00:05:22.06 and comparisons with animals, 00:05:24.10 have started to reveal the genome composition 00:05:26.11 and biology of the first animals, 00:05:28.15 organisms that lived and died 00:05:31.04 almost a billion years ago, 00:05:32.27 and yet by studying living organisms 00:05:34.12 we can learn about how they functioned. 00:05:37.01 In Part II, which I will come to later, 00:05:39.08 I will tell you that some choanoflagellates 00:05:41.22 can transition between being single-celled 00:05:43.26 and multi-celled, 00:05:45.16 and I'll tell you about how that happens, 00:05:47.22 and in addition I will tell you 00:05:50.03 about how that's regulated. 00:05:51.26 There are intrinsic and extrinsic influences on this process. 00:05:54.21 But, let me get back to this big question: 00:05:57.21 how did animals first evolve? 00:06:00.01 And in particular, can we focus on multicellularity? 00:06:03.14 So, let me remind you that 00:06:06.05 animals are not the only multicellular organisms out there. 00:06:08.29 We are only one of many 00:06:11.23 diverse multicellular forms out there. 00:06:13.09 So, of course, we have representative animals, 00:06:15.21 but plants are a remarkable example of multicellularity. 00:06:18.28 There are also green algae, 00:06:20.28 the fungi, 00:06:22.11 and, on the far side of the slide, 00:06:24.12 the slime molds, 00:06:25.23 and there are, you know, 00:06:27.13 probably 20 different lineages that are multicellular, 00:06:30.01 and so each of these lineages 00:06:34.01 has an interesting history in terms of multicellularity 00:06:37.04 and you might think that we could compare 00:06:39.01 among all of these lineages 00:06:40.17 and learn something about the origins of multicellularity, 00:06:43.21 but it turns out that that's not possible, 00:06:46.00 and that's not possible for a few reasons. 00:06:48.05 One is that if we look at the cell biology 00:06:50.14 of each of these different multicellular lineages, 00:06:53.01 we see that their multicellularity 00:06:55.08 is set up differently. 00:06:56.24 So, some organisms like plants and green algae, 00:06:59.19 they have stiff cell walls 00:07:02.20 that mean that a cell is born where it's going to die, 00:07:06.18 they're not able to move around relative to each other, 00:07:08.29 whereas animals and the slime mold 00:07:12.12 don't have a cell wall and the cells are able to move around 00:07:15.09 and resculpt, 00:07:17.05 and that changes their ability to form complex structures 00:07:20.02 and interact with their environment. 00:07:22.17 So, these differences as the cell biological level 00:07:24.23 also help us to understand 00:07:27.03 something that we see at the level of genomes. 00:07:29.15 Now, you might imagine that you could 00:07:32.20 compare the genomes of different multicellular organisms, 00:07:34.26 and the genes they share in common, 00:07:36.22 which are indicated here at the intersection, 00:07:38.17 that these would be the ones involved in multicellularity, 00:07:40.20 but in fact that is not the case. 00:07:42.20 The genes found at the intersection 00:07:44.13 of comparing the genomes 00:07:46.09 of these different multicellular lineages 00:07:48.23 are the genes that are involved 00:07:51.18 in basic housekeeping functions in the cell: 00:07:53.26 DNA replication, translation, repair, etc. 00:07:58.09 The genes that are involved 00:07:59.05 in mediating interactions between cells 00:08:02.04 are actually the genes that are unique 00:08:04.18 within each of these genomes. 00:08:06.11 Why? Why is that the case? 00:08:08.22 Well, to explain why the genes for multicellularity 00:08:12.14 are different in each of these lineages, 00:08:14.07 I need to introduce you to a simple tree. 00:08:17.02 So, what I'm showing you here is 00:08:20.25 a very simple tree depicting the relationships 00:08:23.15 between three different major multicellular lineages 00:08:25.24 -- the animals, 00:08:27.11 which are also called the metazoa, 00:08:29.03 the fungi, which include the mushrooms, 00:08:31.23 and the plants -- 00:08:34.04 and what I hope you can see is that 00:08:36.03 there are a few surprises in looking at this tree. 00:08:38.16 First of all, it's only recently been appreciated 00:08:40.27 that the closest living multicellular relatives of animals 00:08:44.23 are the fungi, 00:08:46.15 but the other thing I need to tell you 00:08:49.01 is that, by looking at diverse organisms, 00:08:51.28 it has now become clear that multicellularity 00:08:54.14 evolved independently in each of these lineages, 00:08:57.12 and that's depicted by these yellow bars. 00:08:59.22 So we think, actually, 00:09:01.15 that the last common ancestor, 00:09:03.13 for instance, of the animals and the fungi, 00:09:05.16 was not multicellular. 00:09:07.09 In fact, it was unicellular. 00:09:09.20 So, we have a rich history 00:09:11.19 of unicellular life 00:09:14.00 before the origin of these different multicellular lineages, 00:09:16.19 and then these lineages evolved multicellularity 00:09:19.08 independently. 00:09:21.06 Well, what are we going to do? 00:09:22.28 How do we operate within this framework 00:09:24.24 to learn anything about the nature 00:09:27.06 of the organisms from which animals first evolved? 00:09:30.05 Well, the way we do that 00:09:31.24 is to try to find lineages 00:09:34.00 between this long-extinct unicellular ancestor 00:09:38.06 and the origin of multicellularity, here, 00:09:40.11 in the animals. 00:09:42.04 And we do that using a group of organisms 00:09:44.12 that sits in this sweet spot on the phylogenetic tree, 00:09:47.10 and these are the choanoflagellates. 00:09:49.22 So, choanoflagellates were discovered long ago 00:09:53.03 and I'm going to tell you 00:09:54.09 quite a bit about them in the next few slides, 00:09:56.04 but I want to say that the evidence for them sitting 00:09:59.19 on this spot on the tree, as the sister group of animals, or metazoa, 00:10:03.13 is that they have shared cell biological features with animals 00:10:07.02 that are not seen anywhere else in diversity. 00:10:09.21 Phylogenetic analyses of diverse genes 00:10:12.12 have indicated that choanoflagellates 00:10:14.20 are the closest living relatives of animals, 00:10:16.18 and then I'm going to tell you, very excitingly, 00:10:18.21 that we've sequenced the genomes 00:10:20.25 of diverse choanoflagellates, 00:10:23.18 and when we compare the composition 00:10:26.04 of choanoflagellate genomes to those of animals 00:10:28.15 it's very clear that they share a very close relationship 00:10:32.24 to animals. 00:10:34.29 Let me tell you about these organisms 00:10:36.15 because you may never have heard about them before. 00:10:39.02 Choanoflagellates are single-celled microbial eukaryotes. 00:10:43.11 They're about the size of a yeast cell, 00:10:45.18 and they have some diagnostic features 00:10:49.04 that tell you that you're looking at a choanoflagellate. 00:10:51.24 They have a spherical or ovoid cell body. 00:10:54.10 At the top of the cell, 00:10:56.18 which we call the apical surface of the cell, 00:10:58.12 they have, as you can see in red here, 00:11:00.23 something that's called a collar, 00:11:02.25 and this is actually the source of the name choanoflagellate. 00:11:07.24 The phrase choano- refers to the collar, 00:11:09.29 and the choanoflagellates 00:11:12.19 also have a long flagellum, 00:11:14.06 and you can reasonably think of these cells 00:11:16.08 as resembling sperm cells, 00:11:18.16 with the addition of this collar. 00:11:20.23 Now, choanoflagellates are actually quite diverse. 00:11:23.18 They can come in many different shapes and forms. 00:11:26.19 So, almost all choanoflagellates 00:11:29.08 have a single-celled phase to their life history 00:11:31.23 as you can see here. 00:11:33.28 And, as I said, all choanoflagellates 00:11:36.10 have a flagellum and collar, 00:11:38.03 but some of them can form beautiful colonial structures, 00:11:41.06 such as you can see here. 00:11:42.26 This species can actually 00:11:45.02 fluctuate between colonial and single-celled, 00:11:47.25 and some of them form very ornate extracellular structures, 00:11:52.12 such as this beautiful organism, 00:11:54.24 which can actually biomineralized silica 00:11:57.00 to form a rigid structure that protects the cell 00:11:59.23 and mediates its interactions with other organisms 00:12:02.16 in the open ocean. 00:12:05.26 Why do choanoflagellates 00:12:08.07 have this combination of the flagellum and the collar? 00:12:11.16 What does that do for the choanoflagellate? 00:12:14.07 Well, let me show you. 00:12:16.00 What you're going to see, this is a movie, 00:12:18.04 and the flagellum is undulating back and forth, 00:12:21.15 and what this does is it actually creates fluid flow, 00:12:24.20 indicated by the arrows, that pulls water 00:12:28.14 along the surface of the collar, 00:12:30.22 and the flagellum pushes water out 00:12:33.25 behind the cell, 00:12:35.20 and so this has two consequences. 00:12:37.25 If the choanoflagellate cell is not attached to anything, 00:12:40.28 the movement of flagellum allows it 00:12:43.25 to swim along through the water column, 00:12:46.23 but that fluid flow also has a second important function, 00:12:49.17 and that is it allows the choanoflagellate 00:12:52.01 to pull bacteria up against the surface of the collar, 00:12:55.01 and so you can see in this picture right here 00:12:58.07 a bacterial cell that's been trapped 00:13:00.18 up against the side of the collar, 00:13:02.12 and so choanoflagellates actually have an important 00:13:04.25 and intimate interaction with choanoflagellates that... 00:13:08.16 errr, sorry, with bacteria... 00:13:10.14 that is essential for their viability. 00:13:13.03 Now, choanoflagellates were actually, 00:13:14.28 although they are not widely known, 00:13:17.04 choanoflagellates were actually first discovered 00:13:19.21 a long time ago, in the mid to late 1800s, 00:13:23.21 and people like Ernst Haeckel and William Saville-Kent 00:13:26.18 were obsessed with choanoflagellates. 00:13:28.29 Saville-Kent actually wrote a large monograph 00:13:32.24 called the Manual of Infusoria, 00:13:34.27 and there are many, many plates dedicated to the choanoflagellates, 00:13:38.23 showing their incredible diversity. 00:13:41.07 And, one of the things that excited Saville-Kent 00:13:44.00 about choanoflagellates 00:13:46.03 was that, to his eye, 00:13:48.15 they were completely indistinguishable 00:13:50.25 from another group of cells that he saw 00:13:53.01 in the natural world, and that was in sponges. 00:13:56.03 So, he noticed this similarity 00:13:58.07 between the morphology of choanoflagellates 00:14:00.09 and the morphology of sponges, 00:14:02.23 and from that he made the argument that 00:14:05.04 choanoflagellates and sponges might be closely related, 00:14:07.28 and you can see that similarity, I think, 00:14:10.09 even more clearly in this electron micrograph, 00:14:16.01 in which you can see, again, a choanoflagellate cell 00:14:18.22 with its cell body, its collar, and its flagellum, 00:14:22.06 and here you can see, in SEM, 00:14:25.15 a group of choanocytes, 00:14:27.25 that's the name for the collar cells in sponges, 00:14:30.21 arranged in a circle, and they're doing the same thing. 00:14:33.29 They're actually creating fluid flow to capture bacteria. 00:14:37.26 And, I think the power... 00:14:41.07 or the organization of these choanoflagellates, 00:14:44.00 or sorry choanocytes, 00:14:46.08 into this choanocyte chamber 00:14:48.14 is actually a very nice demonstration 00:14:50.22 of what happens when an organism becomes multicellular. 00:14:54.23 And so, an example of this, 00:14:56.18 I'm going to just show you in this movie, 00:14:59.01 is that the coordinated action of collar cells in sponges 00:15:03.14 allows for tremendous fluid flow. 00:15:06.19 And so, what you're going to see in this movie, 00:15:09.11 taken by PBS, 00:15:12.26 is that a diver comes in 00:15:15.13 and releases a cloud of fluorescent water 00:15:19.17 just near a sponge, 00:15:21.28 and now watch what the sponge can do with this, 00:15:24.04 just through the movement and activity of choanocytes. 00:15:28.06 So, the diver comes in, 00:15:30.12 this fluorescent dye is released near the sponge, 00:15:33.00 and now as the camera pan back you see that the sponge, 00:15:35.22 which we think of as a very simple organism, 00:15:38.17 is creating coordinated fluid flow 00:15:41.19 and sponges, through this action, are able to 00:15:44.10 capture enormous amounts of bacteria out of the water column. 00:15:50.25 So, choanoflagellates and sponges 00:15:53.20 are using an indistinguishable cell type 00:15:56.13 to capture bacteria out of the water column, 00:15:59.12 and it turns out that cells that resemble 00:16:02.12 choanocytes and choanoflagellates 00:16:04.12 are actually also found in other groups of organisms, 00:16:06.20 including in the form of epithelia and sperm. 00:16:10.04 When we map the distribution 00:16:12.14 of these types of cells, the collar cells, 00:16:14.20 onto a phylogenetic tree, 00:16:16.21 we can infer that because collar cells 00:16:19.27 are widespread within animals 00:16:22.01 and they're also found in all choanoflagellates, 00:16:24.17 then we can reasonably make an inference 00:16:26.24 that choanocytes and collar cells 00:16:29.03 were also present in their last common ancestor. 00:16:31.21 And we can also compare other features 00:16:33.21 of the biology of choanoflagellates and animals 00:16:36.11 within the context of a phylogenetic tree 00:16:38.21 and that brings us to a very exciting point, 00:16:41.00 which is that we can start to make 00:16:43.06 specific inferences about the cell biology 00:16:45.10 and life history of the first animals. 00:16:48.01 So, in this schematic, 00:16:49.21 what I'm showing you is what we now infer 00:16:53.01 to have been the case for the biology of the first animals. 00:16:56.18 We think that it had a simple epithelium, 00:17:00.08 this planar sheet of cells. 00:17:02.24 We think those cells were adhering tightly to each other. 00:17:06.21 We think that some of those cells, at least, 00:17:09.03 were capable of differentiating into collar cells 00:17:11.22 and, importantly, that those cells 00:17:14.02 were actually eating bacteria. 00:17:16.08 So, the first animals were bacterivorous. 00:17:19.13 We think that the first animal 00:17:22.00 also was capable of undergoing apoptosis, 00:17:24.01 or programmed cell death, 00:17:25.29 and that there were different cell types in the first animal, 00:17:28.18 indicative of cell differentiation within the soma. 00:17:33.01 Moreover, it's become clear, 00:17:35.13 by looking at the distribution 00:17:39.16 of different modes of sexual reproduction, 00:17:41.14 sperm and egg in animals, 00:17:44.02 it's become clear that the first animal 00:17:46.26 from which all living animals evolved 00:17:48.26 was capable of undergoing gametogenesis, 00:17:52.05 and that it produced differentiated eggs and sperm 00:17:55.21 and that these merged, in a process of fertilization, 00:17:58.24 to produce a zygote, 00:18:00.29 and then that zygote underwent multiple rounds of cell division 00:18:03.29 and cell differentiation 00:18:05.28 to produce this adult form that I just told you about. 00:18:08.11 So, I think this is an exciting time in which we're starting 00:18:11.19 to see the power of comparative biology, 00:18:13.27 and we can compare the cell biology of choanoflagellates 00:18:16.22 to animals 00:18:18.19 and start to really make specific inferences 00:18:20.16 about the biology of their last common ancestor. 00:18:24.02 Moreover, with the advent of genomic approaches, 00:18:28.02 we can start to learn something 00:18:30.11 about the genome of this organism. 00:18:34.00 Now, choanoflagellates 00:18:36.11 have really been relatively poorly studied 00:18:38.24 by molecular biologists. 00:18:40.18 There was this flurry in the mid-1800s 00:18:43.01 in which people were spending a lot of time 00:18:45.10 looking at and thinking about choanoflagellates 00:18:47.23 and then they were relatively forgotten 00:18:49.23 within the world of molecular biology, 00:18:52.22 and during the molecular biology revolution. 00:18:56.01 And so, one of the first things I did 00:18:58.13 when I started studying choanoflagellates 00:19:00.27 was to collaborate with the Joint Genome Institute 00:19:03.00 and the Broad Institute 00:19:04.17 to sequence the genomes of two different choanoflagellates, 00:19:06.27 Monosiga brevicollis, 00:19:08.23 which so far we have only seen in unicellular form, 00:19:11.14 and S. rosetta, which can be single-celled or colonial. 00:19:15.12 These genomes have a modest number of genes, 00:19:19.05 between 9-12000 genes in their genomes, 00:19:22.03 and we can compare the composition 00:19:24.08 of those genomes with animal genomes 00:19:26.14 to make inferences about the genome of their last common ancestor. 00:19:29.22 In addition, we've recently started sequencing 00:19:34.16 the transcribed and translated genes 00:19:38.23 in the genomes of twenty other 00:19:42.10 additional choanoflagellates that are in culture, 00:19:45.07 and I just want to make the point that 00:19:47.15 there's a lot of diversity in choanoflagellates, 00:19:49.19 and by surveying the genomes 00:19:52.05 of many, many different choanoflagellates 00:19:53.28 we're starting to get an increasingly complete 00:19:56.01 and complex picture 00:19:58.07 of what the genomic landscape of animal origins 00:20:00.18 might have been. 00:20:02.06 Now, I'm not going to tell you about 00:20:04.03 all of the different genes that are found in that ancestral genome, 00:20:06.14 but I do want to summarize some of the exciting findings. 00:20:10.03 When we analyzed these genomes, 00:20:13.03 we particularly focused on genes 00:20:16.06 whose functions are required for 00:20:19.26 animal multicellularity and animal development, 00:20:22.03 and in particular we focused on genes that are required 00:20:24.18 for cells to adhere to each other, 00:20:26.19 genes that are involved in cell signaling, 00:20:28.13 that is, allowing cells to talk to each other 00:20:30.08 and coordinate their functions, 00:20:32.16 genes that are required for gene regulation, 00:20:34.25 which allows one cell to differentiate 00:20:36.19 its function from the other, 00:20:38.25 and genes that are involved in interactions 00:20:41.07 with what's called the extracellular matrix, the ECM, 00:20:44.08 and these are the genes and proteins 00:20:46.16 whose functions allow cells to create this matrix, 00:20:50.27 this structure that provides a landing spot 00:20:54.27 and scaffold for cell-cell interactions. 00:20:57.21 So, we can think about these as being essential functions 00:21:00.00 for animal multicellularity. 00:21:02.17 Many of the genes that are required for these processes 00:21:04.17 in animals 00:21:06.19 had not previously been found in a non-animal before, 00:21:09.14 and now we can ask, if we look at choanoflagellates, 00:21:12.06 what does that tell us about the ancestry of these genes? 00:21:15.15 Are they really animal-specific? 00:21:17.10 Or, might some of these genes 00:21:19.06 have evolved earlier to serve other functions? 00:21:21.24 Now, remember, 00:21:23.04 we have to do this within a phylogenetic framework, 00:21:25.06 and so we're going to ask two different questions. 00:21:29.00 If we are focused on these classes of genes, 00:21:31.14 what fraction of them seem to be restricted to animals? 00:21:35.04 And, what fraction of them 00:21:37.05 are also in choanoflagellates 00:21:38.22 and therefore, we infer, 00:21:40.15 present in their last common ancestor with animals? 00:21:42.25 Some of these genes might have evolved 00:21:45.02 much earlier in the colonial and unicellular 00:21:48.02 progenitors of animals. 00:21:50.11 So, when we do these types of comparisons, 00:21:53.02 and when we did them, it was really quite exciting. 00:21:56.08 I think it helped to motivate 00:21:58.08 a lot of the future study for choanoflagellates, 00:22:00.15 and that's because choanoflagellates 00:22:03.17 turned out to express many different components of the... 00:22:07.29 or, many different genes that are required 00:22:11.12 for the functions that I was just discussing. 00:22:13.29 So, we can find genes that are required 00:22:16.12 for cell signaling in animals, 00:22:18.08 including things like... 00:22:19.27 it's a bit of a chicken soup, 00:22:21.22 but the GPCRs, these are protein coupled receptors, 00:22:24.02 the receptor tyrosine kinases, 00:22:26.09 proto-oncogenes like Src and Csk. 00:22:29.10 We can also find genes whose functions 00:22:32.07 are both necessary and sufficient for allowing cells 00:22:34.11 to stick together. 00:22:35.28 These include the cadherins and C-type lectins. 00:22:38.01 We can find representatives of various transcription factors 00:22:41.18 that are involved in gene regulation, 00:22:43.03 Myc, p53, and Forkhead, 00:22:45.12 and we even find genes that are involved 00:22:48.13 in forming and coordinating the interactions 00:22:52.24 of animals cells with an extracellular matrix. 00:22:55.13 But, remember, 00:22:57.00 we're finding representatives of these genes 00:22:58.21 in non-animals, the choanoflagellates, 00:23:00.27 and so I think an exciting future area of research 00:23:03.08 is to try to figure out 00:23:05.15 how these genes function in choanoflagellates, 00:23:07.25 and try to make inferences 00:23:10.13 about how they might have functioned 00:23:12.07 in our long-ancient progenitors. 00:23:14.17 Now, it was very exciting to find all these animal genes 00:23:17.06 in choanoflagellates, 00:23:18.29 but I think we all need to agree that choanoflagellates 00:23:21.03 are not animals. 00:23:22.21 So, what makes animals different? 00:23:24.20 And, what is exciting is that these genomic interactions... 00:23:28.22 or, sorry, these genomic comparisons, 00:23:30.24 allow us to learn about 00:23:33.27 what types of genes and genomic innovations 00:23:36.12 might have actually contributed to animal origins. 00:23:38.20 And so, when we look at the gene complement of animals 00:23:42.20 and compare it to choanoflagellates 00:23:44.20 we find that there are some genes 00:23:47.02 that thus far have never been found 00:23:49.13 in a non-animal. 00:23:51.06 And so, these are representatives 00:23:53.11 from each of these different 00:23:56.13 groups of processes as well, 00:23:58.17 and they include important genes involved 00:24:00.17 in developmental signaling, 00:24:02.27 one special class of cadherins, 00:24:05.07 the classical cadherins, 00:24:07.06 that are essential for allowing epithelial cells to interact, 00:24:10.19 important and famous developmental patterning genes 00:24:13.21 like the Hox genes, 00:24:15.17 so far have never been found in a non-animal, 00:24:17.19 and very specialized forms of extracellular matrix components, 00:24:21.00 including the Type IV collagens. 00:24:23.19 So, having genome sequences 00:24:26.22 from living organisms 00:24:28.25 has now allowed us to reconstruct, 00:24:30.28 in increasing detail, 00:24:32.06 the genomic landscape of animal origins. 00:24:36.03 So, what I want to say, then, 00:24:39.17 and what I've tried to say in Part I, 00:24:41.26 is that by studying 00:24:45.07 these previously enigmatic organisms, 00:24:47.27 that had been poorly studied, 00:24:50.16 we're starting to grow and develop 00:24:53.01 a new model for animal origins, 00:24:55.12 and we can study these organisms, now, 00:24:58.15 in a modern context to start to learn 00:25:01.07 about animal origins and details. 00:25:03.14 So, what I've told you in this first section 00:25:06.00 is that choanoflagellates, the study of choanoflagellates, 00:25:08.10 has illuminated the cell biology and genome 00:25:11.14 of the progenitors of animals, 00:25:13.19 and told us that those first animals 00:25:16.09 probably ate bacteria and they had collar cells. 00:25:19.02 And, the second important thing that we've learned 00:25:21.05 by studying choanoflagellates 00:25:23.18 is that a remarkable number of genes 00:25:25.10 required for multicellularity in animals 00:25:27.18 actually evolved before the origin of multicellularity, 00:25:31.19 and an exciting future area of research 00:25:33.25 will be to figure out what those genes were doing 00:25:36.23 before they were required for mediating cell-cell interactions. 00:25:41.23 So, that is the completion of Part I, 00:25:44.20 and in Part II 00:25:47.10 I will tell you about a transition to multicellularity 00:25:49.27 that didn't happen hundreds of millions of years ago, 00:25:52.25 but actually happens every day 00:25:55.25 in one particular choanoflagellate, 00:25:58.00 and I'm going to tell you about how that's regulated. 00:26:01.21 Finally, this work wouldn't have been possible 00:26:04.10 without the help of my past and current lab members, 00:26:07.27 and I'm also very grateful to all the collaborators 00:26:10.20 that made all this work possible. 00:26:13.10 Finally, I'm very grateful 00:26:16.07 for the generous support that's come 00:26:18.13 from the National Institutes of Health, 00:26:20.08 the Gordon and Betty Moore Foundation, 00:26:22.02 the Canadian Institute for Advanced Research, 00:26:24.07 and most recently the Howard Hughes Medical Institute. 00:26:26.10 Thank you very much.

00:00:07.22 So, Hello. 00:00:09.01 My name is Nicole King. 00:00:10.11 I'm an investigator in the Howard Hughes Medical Institute 00:00:12.02 and a professor at the 00:00:13.26 University of California at Berkeley, 00:00:15.20 and I'm excited to be here today 00:00:17.17 to tell you about organisms 00:00:19.15 that we study in my laboratory, the choanoflagellates, 00:00:23.01 and tell you about how they interact with bacteria 00:00:24.09 and how these interactions 00:00:26.11 might inform us about animal origins. 00:00:29.27 Now, I want to provide a little bit of introduction 00:00:32.10 to the motivation for the research in my lab. 00:00:34.25 There's been a lot of focus in the past 00:00:37.20 on understanding how different animal body forms diversified, 00:00:41.21 and understanding how different animals 00:00:43.18 are related to each other on the phylogenetic tree. 00:00:45.29 But, in fact, we know relatively little 00:00:47.29 about the nature of the organisms 00:00:49.22 from which animals first evolved, 00:00:51.25 and in my laboratory we're particularly interested 00:00:53.28 in understanding the genomic innovations 00:00:56.19 and the influences of cell biology 00:00:59.29 and interspecies interactions 00:01:01.29 and understanding how that might have contributed 00:01:04.10 to what we call the transition to multicellularity. 00:01:06.13 That is, how did ancestrally unicellular organisms 00:01:10.15 evolve into organisms 00:01:13.05 that are capable of simple multicellularity, 00:01:15.09 such as this hypothetical colony. 00:01:18.26 In Part I of my talk, 00:01:23.22 I previously spoke about how 00:01:26.05 an unusual group of organisms called the choanoflagellates 00:01:29.03 can help us understand animal origins, 00:01:31.24 and I told you that 00:01:34.13 the first animals likely had genes in their genomes 00:01:37.25 that had evolved much earlier. 00:01:39.15 And so, by comparing choanoflagellates to animals, 00:01:43.06 we're learning about the nature of the first animals. 00:01:45.22 In this part of my talk, 00:01:47.29 I'm going to focus on one particular species 00:01:50.16 of choanoflagellate, 00:01:52.15 and I'm going to tell you that this choanoflagellate 00:01:54.09 actually can transition from being single-celled 00:01:56.17 to having simple multicellularity, 00:01:58.29 and I'm going to tell you about how we've been developing this 00:02:01.29 into a new model system 00:02:03.24 so that we can learn about how that transition, 00:02:06.02 from being single-celled to multicellular, 00:02:08.09 is regulated. 00:02:09.23 And, what we don't know now, 00:02:11.19 but we hope to learn, 00:02:13.05 is whether the regulation of multicellularity in this organism 00:02:15.21 might give us specific insights into the ancestry 00:02:18.14 of multicellularity in animals. 00:02:22.08 Now, the organisms that we study 00:02:24.16 are in fact not animals. 00:02:26.18 They are the sister group of animals. 00:02:28.11 They are called choanoflagellates 00:02:30.06 and they sit on this very special part of the phylogenetic tree 00:02:32.26 because they are the closest living relatives of animals. 00:02:36.04 And our understanding that choanoflagellates 00:02:38.19 sit here on the tree, 00:02:40.07 and that they are our, essentially, evolutionary cousins, 00:02:42.04 comes from multiple lines of evidence. 00:02:44.08 It comes from comparisons of the cell biology 00:02:46.15 of choanoflagellates to the cell biology of animals. 00:02:50.02 It comes from many different independent types 00:02:52.11 of phylogenetic analyses. 00:02:54.12 And it comes from comparisons between 00:02:56.24 the genomes of choanoflagellates and the genomes of animals. 00:03:00.05 From all of these different sets of data, 00:03:02.03 it's now become very clear 00:03:04.11 that the study of choanoflagellates, 00:03:06.14 our closest living relatives, 00:03:08.24 tells us about the biology of our last common ancestor. 00:03:14.05 So, I introduced this in Part I, 00:03:16.24 but I just want to quickly 00:03:19.21 review the biology of choanoflagellates 00:03:22.00 because it becomes essential for understanding 00:03:24.00 what I'm about to tell you in the later part of this talk. 00:03:28.09 Choanoflagellates are microbial eukaryotes. 00:03:31.05 They have a spheroid... 00:03:34.05 spherical or ovoid cell body, 00:03:36.14 an apical collar of actin-filled microvilli, 00:03:39.11 and a long apical flagellum. 00:03:41.14 And this flagellum can undulate 00:03:43.26 from side to side, 00:03:45.21 and this undulation creates water currents 00:03:47.26 that allow choanoflagellates 00:03:50.26 to swim through the water column, 00:03:53.22 but these water currents also pull water 00:03:57.27 from the media up against the collar, 00:04:00.04 and those water currents can carry bacteria, 00:04:02.22 and bacteria are actually the primary prey target 00:04:06.10 for choanoflagellates. 00:04:07.28 Choanoflagellates are voracious bacteriovores. 00:04:10.12 They love eating bacteria, 00:04:11.27 they're very good at, 00:04:13.22 and this is an essential part of their biology 00:04:15.28 - their ability to capture and ingest bacteria. 00:04:19.24 So, choanoflagellates have a lot of really interesting aspects 00:04:22.10 to their biology, 00:04:24.13 one of which, obviously, is this ability to eat bacteria, 00:04:27.02 but one of the aspects of their biology 00:04:29.03 which really excited me when I first learned about it 00:04:31.13 as a postdoc 00:04:33.04 is that some choanoflagellates can form 00:04:35.11 these beautiful multi-celled colonies. 00:04:38.04 These colonies are in fact, to me, 00:04:40.18 reminiscent of some types of marine invertebrate embryos, 00:04:44.19 and these colonies 00:04:47.11 raise all sorts of questions about 00:04:49.29 how do the cells interact 00:04:52.03 and how is this process regulated? 00:04:55.05 Moreover, you'll remember that I told you 00:04:58.21 that one of the major questions in my laboratory 00:05:00.28 is how, evolutionarily, 00:05:03.09 did the ancestors of animals evolve the ability 00:05:06.08 to form simple multicellular morphologies. 00:05:08.25 And here we have, in living color, 00:05:11.08 an organism that actually does it, 00:05:13.08 every day. 00:05:15.12 And so, what we've been doing in my laboratory 00:05:17.02 is to understand... 00:05:18.23 is to study this process 00:05:21.07 in minute detail the same way 00:05:24.23 that a Drosophila biologist might try to study 00:05:26.29 how a fruit fly goes from an egg 00:05:29.00 to an embryo to an adult, 00:05:31.23 or a mouse biologist 00:05:34.07 studies the same process of development. 00:05:36.02 We're trying to study, in mechanistic detail, 00:05:38.22 the process by which this organism, S. rosetta, 00:05:41.16 goes from being a single cell 00:05:44.05 to a multi-celled colony. 00:05:46.19 And, in particular, 00:05:47.25 we're focusing on trying to understand 00:05:50.13 the mechanisms of cell adhesion and cell signaling 00:05:52.03 within the colony. 00:05:53.09 We're trying to understand 00:05:54.24 what triggers this transition 00:05:56.13 from being single-celled to colonial, 00:05:58.11 and eventually we hope to learn 00:06:02.00 whether the mechanisms underlying this transition 00:06:03.22 in choanoflagellates 00:06:05.15 are related to mechanisms underlying animal development, 00:06:08.02 in which case we would infer 00:06:10.01 that they are ancient and evolved 00:06:12.07 before the origin and diversification of animals. 00:06:14.23 So, I'm going to tell you a lot 00:06:17.18 about this organism, S. rosetta. 00:06:19.14 And, the first thing I need to tell you 00:06:21.23 is that it does a lot of exciting things. 00:06:24.20 You know, I think many of us think 00:06:26.27 about protozoa as being simple organisms 00:06:31.01 that lead a rather mundane life, 00:06:34.07 but this organism not only can switch between 00:06:37.18 being single-celled and colonial, 00:06:39.20 it actually has a really wild and crazy life history. 00:06:42.18 It has many different morphologies 00:06:45.24 that it can produce, 00:06:47.22 and these are all coming 00:06:51.28 from an organism... 00:06:53.14 a single genotype is encoding 00:06:55.03 for all of these different forms, 00:06:57.09 and many of these forms 00:06:59.10 can differentiate into other forms. 00:07:02.02 So, this cell in the center 00:07:04.02 we call the 'slow swimmer', 00:07:06.08 and cultures that only have slow swimmers in them 00:07:09.03 are capable of producing rosette colonies, 00:07:13.02 chain colonies, 00:07:14.26 fast swimmer cells... 00:07:16.15 and these fast swimmers can differentiate 00:07:18.16 into these attached cells. 00:07:20.20 So, there's a lot of dynamic cell differentiation that's going on, 00:07:23.09 and it seems to have at least some 00:07:26.00 environmental component because we can, 00:07:28.05 in the laboratory, push the choanoflagellate 00:07:30.22 toward different types of cells 00:07:33.14 by changing the environmental conditions 00:07:35.10 in which we grow the cells. 00:07:37.23 For the sake of simplicity 00:07:39.11 and also to focus on things that we know the most about, 00:07:41.16 today, I'm only going to focus on 00:07:44.07 this part of the life history, 00:07:46.16 and try to understand, 00:07:48.25 what is it that allows this cell to differentiate 00:07:52.01 into these other multicellular forms. 00:07:54.16 In particular, 00:07:57.12 we're going to talk about the rosette form, 00:07:59.19 because this is the form in which S. rosetta 00:08:01.28 was actually isolated from nature, 00:08:04.03 and this is the one that is most similar 00:08:07.12 to the multicellular form 00:08:09.22 that we hypothesize 00:08:12.01 was required for the ancestry of animals. 00:08:14.21 So, we want to know, 00:08:16.21 how do rosettes form? 00:08:19.09 Are they forming 00:08:21.14 from multiple cells swimming together and sticking? 00:08:24.14 And that would be similar 00:08:26.05 to the slime mold Dictyostelium... 00:08:28.11 or are they more similar to animals 00:08:30.09 in the way in which they form? 00:08:31.24 That is to say, 00:08:33.12 does a single cell divide repeatedly 00:08:35.11 to form a rosette. 00:08:37.14 We also like to know, 00:08:39.08 how are the cells inside of the rosette 00:08:41.10 adhering to each other? 00:08:42.25 How do you get that stable structure? 00:08:44.20 Again, trying to draw analogies to embryogenesis. 00:08:48.09 And finally, we have this enigma, 00:08:52.09 which is that this single cell 00:08:54.10 is capable of producing three different types of morphologies. 00:08:59.22 It can divide to produce more copies of itself, 00:09:02.14 it can produce these chains, 00:09:05.26 or it can produce rosettes, 00:09:07.29 and we'd like to know 00:09:10.01 how is that differentiation process regulated. 00:09:13.14 So, let me start with question number 1: 00:09:15.13 how are these rosettes forming? 00:09:18.07 To investigate this 00:09:19.26 we used multiple different approaches, 00:09:21.23 but I think the simplest one is to just watch, 00:09:24.09 and what we found is that 00:09:27.00 when cultures were shifting 00:09:29.07 from having only single-celled individuals 00:09:31.29 to rosettes 00:09:34.11 it always happened through cell division. 00:09:36.29 And so, what you're going to see in this movie here 00:09:39.15 is that this is a founding cell that's going to divide repeatedly 00:09:42.23 to produce a spherical multi-celled colony. 00:09:45.18 So let's watch. 00:09:48.05 The single cell divides over and over again. 00:09:50.12 The cells remain attached, 00:09:52.18 and in the end of this 15 hour movie 00:09:55.28 we have a spherical colony. 00:09:58.01 And, this I think is also nicely shown here 00:10:00.10 in these stills taken by confocal microscopy. 00:10:04.04 Now, I want to make the point 00:10:06.27 that even though this looks 2-dimensional, 00:10:08.24 these colonies are actually 3-dimensional 00:10:10.23 and are producing a nice sphere. 00:10:14.06 Okay, so, the answer to our first question, then, 00:10:16.11 is that the rosettes are forming through cell division, 00:10:19.12 and that provides a very nice parallel 00:10:21.21 to the way in which embryos of animals form, 00:10:24.12 in which you have a single cell, the zygote, 00:10:27.03 and that zygote divides over and over again 00:10:29.07 to produce a multicellular embryo. 00:10:31.20 How are the cells in choanoflagellate colonies 00:10:34.22 actually sticking together? 00:10:36.11 And, to answer this, 00:10:38.14 we had to use electron microscopy. 00:10:41.14 If you look at choanoflagellate cells 00:10:43.20 using a scanning electron microscope, 00:10:45.29 what you see is that the cells are actually connected 00:10:49.11 by these fine intercellular bridges that you can see here, 00:10:52.28 and we think, although we don't know yet, 00:10:55.20 but we think that these are the product of 00:10:57.27 incomplete cytokinesis. 00:10:59.13 That is to say that the cleavage plane 00:11:01.14 that forms when cells are dividing 00:11:03.25 doesn't close completely, 00:11:05.09 and so there's a little remnant of membrane 00:11:07.23 that remains between those cells 00:11:10.01 and it produces this intercellular bridge. 00:11:14.11 But that's not the only source of cell adhesion 00:11:17.13 between these cells. 00:11:20.07 If you examine the cells under different conditions, 00:11:22.25 and then look at them either in SEM or in TEM, 00:11:27.28 what you can see is that there is 00:11:30.21 a fine meshwork of material covering the cells 00:11:33.12 and also filling the inside of the colony, 00:11:35.25 and this is actually extracellular matrix, or ECM. 00:11:38.29 And so, it's the combination of the intercellular bridges 00:11:45.07 and extracellular matrix 00:11:47.14 that is contributing to the structural integrity of the rosette. 00:11:51.21 Okay, so just to summarize, then, 00:11:53.18 I've just told you that when choanoflagellates form... 00:11:56.26 when S. rosetta forms rosette colonies 00:11:59.20 it forms it through incomplete cytokinesis, 00:12:02.05 and what I've also told you 00:12:05.00 is that the cells in these rosettes 00:12:06.22 are adhering through a combination 00:12:08.17 of intercellular bridges and extracellular matrix, 00:12:11.14 but of course I think the question 00:12:13.18 we should all be interested in and wondering about is, 00:12:16.24 how is this transition regulated? 00:12:19.28 And what determines 00:12:22.18 whether this single-celled form of S. rosetta 00:12:25.17 divides to produce more of itself, 00:12:28.15 or produces chains, 00:12:30.25 or produces rosettes? 00:12:32.20 What is determining the regulation 00:12:35.03 of this developmental switch? 00:12:37.10 And here's where I was really stymied in my research. 00:12:40.01 And so, what I need to tell you 00:12:42.16 is a story of frustration 00:12:45.04 that finally ended with serendipity 00:12:47.08 and I think an exciting new discovery. 00:12:50.27 So, let me back up and tell you 00:12:53.23 about how I started studying S. rosetta. 00:12:56.13 When I began my postdoc, 00:12:58.06 there were no labs out that were studying choanoflagellates, 00:13:01.25 and so I was fortunate to be taken into the lab 00:13:04.18 of a leading evo-devo researcher, 00:13:07.14 Sean Carroll, 00:13:09.06 but I had to go to the ATCC, 00:13:11.03 the American Type Culture Collection, 00:13:13.17 to work with a protistologist named Tom Nerad, 00:13:16.06 to learn how to study choanoflagellates. 00:13:18.00 And while I was there, 00:13:19.27 he and a group of other scientists 00:13:21.28 were studying diverse microbial eukaryotes 00:13:23.21 from the environment, 00:13:25.16 and he observed one choanoflagellate 00:13:27.08 that was capable of forming beautiful rosette colonies, 00:13:30.08 and this is S. rosetta. 00:13:32.12 So, he was kind enough to put S. rosetta into culture. 00:13:35.29 He isolated a single colony, grew it up, 00:13:38.18 and froze it down so that I could study 00:13:41.07 S. rosetta in perpetuity. 00:13:43.07 So, I brought it back to Madison, 00:13:45.10 where I was doing my postdoc, 00:13:47.02 and started growing this choanoflagellate. 00:13:49.02 And, let me tell you, 00:13:51.01 it was a very frustrating finding when I brought it back to Madison, 00:13:54.22 because S. rosetta cultures, in the laboratory, 00:13:57.29 rarely have rosettes. 00:13:59.24 They were largely unicellular, 00:14:01.22 and so you can see, here would be a best case scenario. 00:14:03.29 Lots of single-celled choanoflagellates, 00:14:06.04 you can see the round cells, 00:14:08.20 and only the occasional rosette colony, 00:14:11.28 and lots of bacteria. 00:14:13.20 And so, no matter what I did, 00:14:16.08 these cultures would not robustly form rosette colonies, 00:14:18.24 and so that meant that I wasn't going to be able 00:14:23.07 to do the types of experiments that I wanted to do 00:14:24.28 to study the mechanisms of rosette development. 00:14:27.26 So, I worked on this for a long time, 00:14:29.22 without success, 00:14:31.21 and then ended up bringing... 00:14:33.25 fortunately, other things worked, 00:14:36.11 but S. rosetta was recalcitrant, 00:14:38.21 and so I brought it with me when I started my own lab at Berkeley 00:14:41.24 and continued to experience frustration, 00:14:46.12 and continued to be unable 00:14:49.10 to get this thing to form rosettes 00:14:51.08 in any robust or predictable way. 00:14:53.06 And so, finally, I switched my research objectives 00:14:56.17 and decided that if I couldn't get rosette colonies 00:15:00.05 from this species, 00:15:02.12 at least I could sequence its genome, 00:15:04.09 and that might tell me something, 00:15:06.00 by comparing its genome to the 00:15:08.03 genomes of single-celled choanoflagellates, 00:15:09.11 might tell me something about the mechanisms regulating development. 00:15:12.17 And so, an undergraduate in the lab at the time, 00:15:15.03 Rick Zuzow, helped me to get this choanoflagellate 00:15:17.07 ready for genome sequencing, 00:15:19.17 and at one point... 00:15:20.20 one challenge I need to point out is that 00:15:22.21 because choanoflagellates eat bacteria, 00:15:24.29 this creates a real problem for genome sequencing 00:15:27.11 because the bacterial DNA 00:15:30.27 can make it difficult 00:15:34.29 to get a high-quality genome assembly from the choanoflagellate. 00:15:38.02 So, the first thing he had to do, then, 00:15:40.03 was to treat these cultures with cocktails of antibiotics, 00:15:45.24 and he tried two different cocktails of antibiotics 00:15:49.12 and they gave two very interesting results. 00:15:51.28 So, one cocktail of antibiotics, 00:15:54.11 actually, when he treated, when he used that, 00:15:57.28 it resulted in a culture that had a bloom of rosette development. 00:16:00.23 And so, you can imagine, we were thrilled! 00:16:03.00 It was so exciting and we had no idea 00:16:05.15 why this treatment with antibiotics 00:16:08.05 led to rosette development, but it did. 00:16:11.08 Perhaps even more interestingly, 00:16:13.08 when he treated with a different cocktail of antibiotics, 00:16:17.01 he recovered a culture that produced no rosettes, ever. 00:16:21.09 And so, we find that... 00:16:23.24 we found that different cocktails of antibiotics 00:16:26.04 led to different results, 00:16:29.14 and we started to wonder what was going on. 00:16:32.12 Now, it could have been 00:16:35.06 any of a number of possible explanations. 00:16:37.25 It could have been that the antibiotics 00:16:40.15 were directly stressing the choanoflagellates in different ways. 00:16:43.10 It could be that the choanoflagellates 00:16:45.13 were starving 00:16:48.27 when exposed to one set of antibiotics, but not the other. 00:16:51.20 But, it was hard to reconcile these different observations, 00:16:54.08 but the one possible explanation 00:16:57.12 that sort of was consistent with what we were seeing 00:17:00.11 was the possibility that bacteria from the environment 00:17:03.06 were actually regulating the switch to rosette development. 00:17:06.06 And so, to test that, 00:17:08.06 Rick took bacteria from the original environmental sample 00:17:11.15 and added them to this culture 00:17:14.01 that didn't form rosettes, 00:17:16.08 and asked whether those environmental bacteria 00:17:19.17 could stimulate rosette development 00:17:21.17 in these non-rosette forming cultures. 00:17:23.19 And, in fact, that did work. 00:17:26.22 So, environmental bacteria 00:17:29.00 were sufficient to induce rosette development. 00:17:31.20 So, that was very exciting, 00:17:33.21 very unexpected, 00:17:35.11 and of course the next thing we wanted to know was, 00:17:38.05 which bacteria were actually 00:17:41.19 providing this stimulus for rosette development? 00:17:44.00 And so, what Rick and other members of the lab did 00:17:47.00 was to go into this original environmental sample 00:17:48.29 and isolate multiple independent strains of bacteria 00:17:54.25 and test them one at a time 00:17:57.07 in this rosette-deficient culture, 00:17:59.10 and ask whether those bacteria 00:18:01.22 were capable of inducing rosette development. 00:18:04.20 And so, we tested 64 different environmental isolates, 00:18:09.12 one at a time, 00:18:11.12 and what we found in the end was that, 00:18:13.07 of all of these, only one species 00:18:15.13 was capable of inducing rosette development. 00:18:19.00 So, what was that species? 00:18:22.14 It was the previously undescribed 00:18:25.12 bacterial speices Algoriphagus machipongonensis. 00:18:29.01 So, we can add Algoriphagus to cultures 00:18:32.05 of single-celled choanoflagellates, 00:18:34.02 and that is sufficient to induce them 00:18:36.02 to form rosette colonies. 00:18:38.04 I need to make a couple of important points 00:18:40.12 about Algoriphagus. 00:18:42.22 First of all, it was co-isolated with S. rosetta, 00:18:45.03 so it's a natural environment co-habitant with S. rosetta, 00:18:49.00 and it's also a sufficient prey target. 00:18:52.13 So, we can grow S. rosetta 00:18:54.25 only in the presence of Algoriphagus 00:18:56.24 and it's perfectly viable 00:18:58.21 and it happily form rosette colonies. 00:19:00.26 The other exciting and interesting thing about Algoriphagus 00:19:03.22 is that it's a member of a much larger group of bacteria 00:19:06.04 called the Bacteroidetes, 00:19:08.15 and Bacteroidetes bacteria 00:19:11.15 are some of the most abundant bacteria in your gut, 00:19:14.06 and they're also abundant and important bacteria 00:19:17.09 in diverse environmental settings, 00:19:19.16 including the oceans and soil. 00:19:22.08 And, in each of these settings, 00:19:24.01 there's a growing interest in the ways in which 00:19:26.15 bacteria might be influencing the biology of eukaryotes 00:19:29.07 with which they're associated. 00:19:31.15 So, we're excited about the possibility 00:19:34.02 that this interaction which I've just described to you 00:19:36.12 might be used to help understand 00:19:39.16 the mechanisms underlying interactions 00:19:41.10 between bacteria and eukaryotes. 00:19:43.26 Now, why... 00:19:46.01 why would we be so excited about bacteria? 00:19:47.27 And I've hinted at that a little bit, 00:19:49.13 but I want to tell you... 00:19:51.05 I want to back up and give you a little bit of context 00:19:53.03 for why bacteria are such an important factor 00:19:58.08 to try to investigate 00:20:00.12 when you're thinking about animal origins. 00:20:01.23 And, to do that, I need to go in the way-back machine. 00:20:04.06 I need to remind you about the history of life on Earth. 00:20:08.06 And, to that do, 00:20:10.13 I'm going to use this time chart 00:20:12.13 in which we're thinking about life, the history of life, 00:20:14.07 starting with the present here on the top, 00:20:16.09 going back to the start of Earth 00:20:19.09 and the solidification of the crust, 00:20:21.13 and say that we think that the last universal common ancestor 00:20:24.25 of life 00:20:26.16 lived on the order of over 3 billion years ago. 00:20:29.05 And, the earliest fossil evidence 00:20:32.00 we have for life 00:20:34.00 is that of stromatolites. 00:20:36.16 These are large multicellular 00:20:38.26 aggregations of bacteria. 00:20:40.23 They are essentially a bacterial biofilm, 00:20:43.01 and we preserve representatives of these types of morphologies, 00:20:46.17 here, today. 00:20:48.25 Here is an example of a modern stromatolite, 00:20:50.26 and these complex forms 00:20:53.10 are produced by bacteria, 00:20:55.16 and there's a lot of really terrific work 00:20:57.19 that's being done to address 00:21:01.00 the ways in which bacterial metabolism 00:21:04.04 has influenced the geochemistry of Earth, 00:21:07.23 but also the life of other organisms. 00:21:10.27 And, what we now realize, 00:21:13.26 is that animals whose fossils 00:21:17.05 have not been recovered... 00:21:19.01 you know, the oldest animal fossils 00:21:21.16 are no older than about 5-600 million years old 00:21:24.17 and the oldest multicellular eukaryotes in general 00:21:27.14 are on the order of a billion years old, 00:21:29.16 those multicellular eukaryotes 00:21:31.20 evolved in environments that were already dominated 00:21:36.10 by teeming hoards of bacteria. 00:21:38.22 If we're going to understand the origin 00:21:40.24 of multicellular eukaryotes, 00:21:42.20 we need to understand how their progenitors 00:21:45.02 coped with a world 00:21:47.09 that was already populated and colonized by bacteria. 00:21:51.19 So, that's one important point that I want to make 00:21:53.21 about the bacterial context of animal origins. 00:21:56.18 The second point that I want to make 00:21:58.20 harkens back to something I talked about in Part I, 00:22:01.02 and that is that, 00:22:02.19 through the study of choanoflagellates, 00:22:04.09 we've been able to reconstruct 00:22:06.14 some important aspects of the biology of the first animals. 00:22:08.29 And so, you may remember that I mentioned 00:22:11.02 that we think the first animals 00:22:13.08 probably had collar cells 00:22:15.06 and, more importantly, 00:22:17.28 that those first animals were involved in bacterivory, 00:22:21.05 that is to say, they ate bacteria. 00:22:23.08 They make a living by eating bacteria. 00:22:25.15 And so, we now know think that interactions with bacteria 00:22:29.03 were an obligate part of the life history 00:22:31.17 of the first animals. 00:22:33.28 The final point that I want to make 00:22:38.28 is that, if you look at living animals, 00:22:41.19 what you can see is that development 00:22:43.25 in many of these diverse organisms 00:22:45.27 is regulated by bacterial signals. 00:22:48.19 The challenge in these cases... 00:22:50.18 now, obviously, there's been a lot of interest, 00:22:52.28 but the challenge has been that we're looking at 00:22:55.05 large, complex multicellular organisms 00:22:57.28 that are growing in association 00:23:00.04 with diverse and complex communities of microbiota, 00:23:04.19 and this has made it very difficult 00:23:06.22 to try to learn something about the mechanisms 00:23:08.29 underlying these important interactions. 00:23:11.25 And so, what we are now doing 00:23:15.02 is using this interaction 00:23:17.21 between the bacteria Algoriphagus and the choanoflagellate S. rosetta 00:23:21.01 as a simple bioassay 00:23:24.09 to discover bacterial signaling molecules 00:23:26.11 that we think will help us understand 00:23:28.20 the regulation of this developmental switch, 00:23:31.16 but will potentially have relevance 00:23:33.29 to other systems as well. 00:23:35.20 Now, I have to say that 00:23:38.01 this has been a very exciting but also challenging process, 00:23:41.15 in part because we had absolutely no idea 00:23:44.03 what the nature of the signaling molecules were. 00:23:48.20 After casting about in the dark for a little while, 00:23:51.14 we had a hint that came from looking 00:23:55.06 at what is unusual about the Bacteroidetes, 00:23:57.11 which are the bacteria... the large group of bacteria 00:23:59.22 of which Algoriphagus is a member. 00:24:03.25 So, Bacteroidetes 00:24:06.25 actually have, like other members of this group, 00:24:08.20 an outer membrane and an inner membrane. 00:24:11.28 They have components called LPS and peptidoglycan, 00:24:14.17 which are known inducers 00:24:18.09 of immune system components in animals, 00:24:22.04 but they also have an unusual group of lipids 00:24:24.18 called the sphingolipids 00:24:26.23 and the closely related sulfonolipids, 00:24:28.29 and I say that these are unusual, 00:24:30.26 but in fact they're quite common in eukaryotes. 00:24:32.29 It's in bacteria in which 00:24:36.15 you don't often see these types of lipids. 00:24:39.13 And so, for a variety of reasons, 00:24:42.02 we focused on this group of lipids as a potential source 00:24:45.12 of the signaling activity. 00:24:48.01 And, to do this, 00:24:50.14 we have established really one of the best collaborations 00:24:53.27 in my career. 00:24:55.12 It's been a fantastic experience. 00:24:57.01 We're been collaborating with Jon Clardy, 00:24:58.24 who's at Harvard Medical School 00:25:01.01 and has done fantastic work in many systems 00:25:04.17 in recovering bioactive molecules. 00:25:07.07 And so, what he and his group did 00:25:10.10 was they took Algoriphagus, 00:25:12.18 they extracted the sphingolipid fraction 00:25:16.10 from its outer membrane, 00:25:18.13 and then... 00:25:21.21 these sphingolipids are very difficult to deal with, 00:25:23.20 so at our first pass, 00:25:25.23 we've now started using different approaches, 00:25:28.01 but in the fist pass people from his lab 00:25:31.18 used a process called prep-TLC, 00:25:34.05 and this is thin layer chromatography, 00:25:36.19 to separate out all those sphingolipids, 00:25:39.28 and then they would scrape them off of this plate 00:25:43.01 and send them to my lab where we would test them 00:25:45.00 in the bioassay 00:25:46.27 and see whether those fractions were capable of 00:25:49.23 inducing rosettes or not. 00:25:51.10 And, based on that, 00:25:53.03 then we could take the fractions that were capable of inducing 00:25:55.23 and analyze them by mass spectroscopy. 00:25:58.25 And so, this was an iterative process. 00:26:01.09 We would send the bacterial samples, 00:26:03.09 they would fractionate them, 00:26:04.27 they would send us the fractions, 00:26:06.20 we would test them, we would send them the information... 00:26:08.02 it was back and forth, 00:26:11.01 and through a long series of analyses 00:26:13.23 we eventually were able to identify 00:26:15.18 the first bacterial molecule that was capable 00:26:18.12 of inducing rosette development 00:26:20.15 and that is this molecule. 00:26:22.17 We've name it RIF-1 for rosette-inducing factor 1, 00:26:25.00 and we now have a structure for it, 00:26:26.23 which is very exciting, 00:26:28.18 and we also know something about its chemistry. 00:26:31.28 So, RIF-1 is not a sphingolipid. 00:26:35.01 It is in fact in a different class of molecules 00:26:37.16 called the sulfonolipids, 00:26:39.14 and the sulfonolipids differ from sphingolipids 00:26:42.23 in that they have a sulfonic acid headgroup 00:26:45.13 at one end. 00:26:47.16 This class of molecules 00:26:50.09 has not previously been shown to be involved in signaling, 00:26:52.21 so this is exciting because it's the tip of the iceberg. 00:26:55.04 These types of molecules 00:26:57.09 might have wide-ranging roles 00:26:59.05 and we can just start to study them now. 00:27:01.06 What is known is that, in bacteria, 00:27:03.06 they seem to have a role in regulating gliding motility. 00:27:07.28 So, this molecule 00:27:11.01 we can fractionate and isolate from bacteria, 00:27:12.26 but it is actually functioning in a way 00:27:15.10 that is consistent with it having a real role in the environment. 00:27:18.09 And so, we took purified RIF-1 00:27:21.11 and tried to determine 00:27:24.15 the concentration of the molecule 00:27:26.13 that was required to induce rosette development, 00:27:28.19 and the exciting result is that in fact 00:27:32.03 RIF-1 is tremendously potent. 00:27:34.14 It is able to induce rosette development... 00:27:36.21 here again I'm showing you 00:27:39.10 the extent of rosette development along the y-axis 00:27:41.25 and the concentration of RIF-1 along the x-axis, 00:27:46.09 and what I hope you can see is that 00:27:48.00 we are getting maximal induction of rosette development 00:27:50.22 at concentrations that are in the femtomolar range, 00:27:54.16 and so this... 00:27:56.10 not only is it active at these levels, 00:27:58.12 but these are the levels in which we find RIF-1 00:28:01.19 in the conditioned media, 00:28:03.09 and so the activity of RIF-1 is entirely consistent 00:28:06.03 with it having an important function 00:28:08.09 at environmental concentrations. 00:28:10.04 So, that was very exciting. 00:28:11.27 So, it's a new class of signaling molecule, 00:28:13.22 it's active at environmentally-relevant concentrations, 00:28:16.26 that's all good, but now we get to the nitty-gritty. 00:28:20.01 I want to show you that, in fact, 00:28:22.08 the maximal induction that we're seeing 00:28:24.07 is only on the order of about 5% of cells 00:28:27.04 going into rosettes, 00:28:29.02 so it suggests that RIF-1 is important, 00:28:31.00 it's sufficient for rosette induction, 00:28:32.28 but it's not the whole story. 00:28:34.27 And so, what we've now done 00:28:37.20 is go back to our simple bioassay 00:28:39.20 to see, now, if we can more rapidly discover 00:28:42.00 other potential bacterial signaling molecules, 00:28:44.15 and in fact we have. 00:28:47.15 So, again this is through our collaboration 00:28:49.16 with the Clardy lab. 00:28:51.01 We've gone back now 00:28:53.09 and analyzed more broadly, 00:28:55.07 not just the sphingolipids, 00:28:57.11 but the entire lipid fraction, 00:29:01.02 and we've been able, through this process, 00:29:02.27 to find other bioactive signaling molecules. 00:29:05.19 Here in this part of the eluate we find RIF-1, 00:29:10.24 but also many, many other sulfonolipids, 00:29:13.15 all of which are inactive, 00:29:15.08 and that makes an important point. 00:29:17.02 RIF-1 isn't active because it's a sulfonolipid. 00:29:19.22 RIF-1 is a special sulfonolipid. 00:29:22.09 Most other sulfonolipids can't induce (rosette development). 00:29:25.25 So, there's a tight structure-activity relationship 00:29:28.00 between RIF-1 and its ability to regulate rosette development. 00:29:31.11 But, what we've also found is that there are 00:29:33.28 other classes of sulfonolipids 00:29:36.04 that are structurally similar to RIF-1 00:29:38.00 that are also capable of inducing. 00:29:40.07 There's an entirely different class of lipids 00:29:42.16 called the LPEs, or the lysophosphatidylethanolamines. 00:29:45.22 These are able to synergize with RIF-1 00:29:48.18 and the other sulfonolipids 00:29:50.17 to promote rosette development. 00:29:52.18 And finally, there's another type of lipids 00:29:54.29 that's an antagonist of the RIFs, 00:29:58.07 and if you incubate it with the choanoflagellate 00:30:02.03 and then add RIF-1, -2, or -3, 00:30:04.23 you find that you block rosette development. 00:30:07.05 So, there are many different, diverse bioactive lipids 00:30:10.08 available in Algoriphagus, 00:30:12.15 and we can mix them together 00:30:14.17 and reconstitute the full induction activity 00:30:17.00 that you normally get from live Algoriphagus bacteria. 00:30:21.02 So, there are diverse bioactive molecules 00:30:23.13 that we have discovered already using our bioassay, 00:30:26.04 just from Algoriphagus, 00:30:27.26 but in addition 00:30:30.13 we've also surveyed lots of other diverse bacteria, 00:30:33.13 and biologists will do this and what I'm going to tell you is, 00:30:36.01 I'm showing you a phylogenetic tree of diverse bacteria 00:30:39.05 and you don't need to worry about the fact that 00:30:41.20 you can't read which bacteria I'm showing you. 00:30:43.24 The point I want to make is that there's a lot of diverse bacteria 00:30:45.27 we've tested now, 00:30:47.26 and shown in these squares 00:30:50.04 I'm indicating whether they induce rosettes or not. 00:30:53.04 Those shown with black do induce. 00:30:54.29 Those shown with white don't, 00:30:57.25 and those in grey induce at a low level. 00:31:00.03 And so, we're find that across the tree of bacterial diversity, 00:31:02.28 we're finding many different bacteria 00:31:05.28 that induce and some of them seem to use 00:31:08.12 different types of bioactive molecules 00:31:10.22 to induce rosette development. 00:31:13.00 Finally, we'd like to know 00:31:15.16 whether this bioassay might help us 00:31:18.07 find something that's of biomedical relevance, 00:31:20.02 and so we've actually surveyed 00:31:22.18 the bacteria of the vertebrate gut system, 00:31:24.23 looking at different parts of the intestinal tract, 00:31:27.13 and testing whether they're capable of 00:31:29.28 inducing rosette development, 00:31:31.20 and we find, in fact, that they can. 00:31:33.17 So, bacteria from the stomach and the small intestine 00:31:35.29 do not induce rosette development, 00:31:38.08 but bacteria from the cecum and the colon do, 00:31:41.12 and if we follow the strategy that we followed previously 00:31:44.04 in the discovery of Algoriphagus, 00:31:46.14 we can do it here 00:31:48.27 and culture these bacteria and see if we can identify 00:31:51.05 the species that induce rosette development, 00:31:53.12 and so we've done that, 00:31:55.08 and we've now discovered the specific bacteria 00:31:57.10 from the gut system 00:31:59.06 that are capable of inducing rosette development 00:32:00.27 and we're focusing on isolating the bioactive molecules 00:32:03.27 from these organisms as well. 00:32:06.25 Okay, so let me just recap what I've told you. 00:32:10.16 I've told you that rosette development is regulated... 00:32:13.21 is the process of incomplete cytokinesis, 00:32:16.24 and cells in rosettes 00:32:19.04 are held together through a combination 00:32:21.24 of intercellular bridges and ECM. 00:32:24.09 Moreover, what we're discovered, 00:32:26.00 and it was quite unexpected, 00:32:28.04 we found that the developmental switch 00:32:30.07 that controls whether a single cell 00:32:32.10 is going to form a rosette, chain colonies, 00:32:35.26 or another single cell, 00:32:37.20 that's regulated not solely by genetics 00:32:40.18 of the choanoflagellate, 00:32:42.09 but actually, importantly, 00:32:44.18 by signals that are released 00:32:47.02 by environmental bacteria. 00:32:50.24 So, over Part I and Part II, 00:32:53.27 I've been telling you about these 00:32:56.18 really interesting organisms, the choanoflagellates, 00:32:59.16 that were discovered in the 1800s, 00:33:01.29 that we've now brought into the molecular 00:33:03.23 and genomic era. 00:33:05.15 And, through the study of choanoflagellates, 00:33:06.28 we're finding that we're able to reconstruct 00:33:09.02 the biology of the first animals 00:33:11.28 in increasingly resolution, 00:33:13.29 and one of the most exciting things 00:33:16.11 I think we've found through these types of studies 00:33:18.20 is that many of the genes that are essential 00:33:20.27 for regulating cell-cell interactions in animals 00:33:23.21 and regulating the process of development 00:33:26.08 actually evolved before the origin of animals 00:33:29.00 and are conserved in the genomes 00:33:30.28 of living choanoflagellates. 00:33:32.13 So, that's been great, 00:33:34.05 to learn that choanoflagellates provide this window 00:33:36.00 into animal origins. 00:33:38.27 In addition, I told you about 00:33:42.00 a transition to multicellularity 00:33:44.02 that actually happens in the life history of 00:33:46.04 a living choanoflagellate, the choanoflagellate S. rosetta. 00:33:49.06 And, the very exciting discovery that we've made 00:33:52.03 by studying this process in mechanistic detail 00:33:56.02 is that the developmental switch 00:33:59.00 to form multicelled rosette colonies 00:34:01.08 is actually regulated by environmental bacteria. 00:34:04.23 So, it's been very exciting, 00:34:07.04 we've been collaborating with Jon Clardy 00:34:09.11 to uncover bioactive molecules, 00:34:11.06 and this now bring us to the point in which 00:34:13.24 we can start thinking 00:34:15.10 about the choanoflagellate side of the story. 00:34:16.03 How is it that choanoflagellates 00:34:18.09 are actually sensing these bacterial signaling molecules? 00:34:21.12 Moreover, we're curious about whether this interaction 00:34:24.25 is something special to the choanoflagellate lineage 00:34:28.01 or whether it actually is informative 00:34:30.06 about mechanisms underlying animal origins. 00:34:32.21 And so, to that end, 00:34:33.29 in the long run we'd like to know 00:34:36.06 whether the mechanisms regulating this signaling interaction 00:34:40.15 between bacteria and choanoflagellates 00:34:43.03 might be conserved in the interactions 00:34:45.06 between animals and their commensal bacteria. 00:34:49.00 So, it's been a real pleasure 00:34:51.10 telling you about this work 00:34:53.07 and I want to take this opportunity to thank 00:34:55.12 a number of people, many of which, 00:34:58.11 you know, I can't list all of them, 00:35:00.00 but I really want to thank everybody in my lab 00:35:01.26 and I've highlighted here, in yellow, 00:35:03.26 the people who have actually contributed to the work 00:35:05.21 that I discussed here. 00:35:07.17 One current member, Arielle Woznika, 00:35:09.11 and many different alumni 00:35:11.29 who have been essential to this project. 00:35:14.05 Moreover, I have to express my gratitude 00:35:17.10 to Jon Clardy, 00:35:19.19 who's been a really fantastic collaborator 00:35:21.05 and I've learned so much from him 00:35:23.02 and it's been a wonderful experience, 00:35:24.29 and then of course our funding agencies. 00:35:26.29 If you find yourself fascinated by choanoflagellates 00:35:28.29 and you want to learn more, 00:35:32.17 we invite many, many people, we want to grow this community, 00:35:35.02 and you can learn more about choanoflagellates 00:35:37.13 in these various locations, 00:35:39.06 and importantly we have a choanoflagellate workshop 00:35:41.10 every two years, so please come and join us. 00:35:44.17 And it's been a pleasure talking to you.

Talk Overview

Animals, plants, green algae, fungi and slime molds are all forms of multicellular life, yet each evolved multicellularity independently. How did animals evolve from their single-celled ancestors? King addresses this question using a group of fascinating organisms called choanoflagellates. Choanoflagellates are the closest living relatives to animals; they are single-cell, flagellated, bacteria eating organisms found between fungi and animals on the phylogenetic tree of life. By sequencing the genomes of many choanoflagellate species, King and her colleagues have discovered that some genes required for multicellularity in animals, such as adhesion, signaling, and extracellular matrix genes, are found in choanoflagellates. This suggests that these genes may have evolved before the transition to multicellularity in animals.

The choanoflagellate S. rosetta can exist as a unicellular organism or it can switch to form multicellular colonies. In fact, its life cycle can be quite complex; it can form long chain colonies, spherical colonies called rosettes, or exist in different unicellular forms. In part 2 of her talk, King explains how she chose to use S. rosetta as a simple model for animal origins. After overcoming the technical difficulty of getting S. rosetta to form rosettes in the lab, she investigated how rosettes develop and how the cells within a rosette adhere to each other. She also asked the intriguing question “What regulates rosette development?”. It turns out that rosette formation is regulated by lipids produced by environmental bacteria that S. rosetta eat. This result adds to the growing interest in how bacteria may be influencing the behavior of diverse animals including humans.

Speaker Bio

While fossils sparked Nicole King’s childhood interest in evolution, she realized that the fossil record doesn’t explain fully how animals first evolved from their single celled ancestors. To answer this question, King decided to study modern day choanoflagellates. Choanoflagellates are single celled organisms that can also develop into multicellular assemblages. King first learned about choanoflagellates… Continue Reading

Educators

About Us

This material is based upon work supported by the National Science Foundation and the National Institute of General Medical Sciences under Grant No. MCB-1052331.

Any opinion, finding, conclusion, or recommendation expressed in these videos are solely those of the speaker and do not necessarily represent the views of iBiology, the National Science Foundation, the National Institutes of Health, or other iBiology funders.